Quantification of prefrontal cortical neuronal ensembles following conditioned fear learning in a Fos-LacZ transgenic rat with photoacoustic imaging in Vivo.

Understanding the neurobiology of complex behaviors requires measurement of activity in the discrete population of active neurons, neuronal ensembles, which control the behavior. Conventional neuroimaging techniques ineffectively measure neuronal ensemble activity in the brain in vivo because they assess the average regional neuronal activity instead of the specific activity of the neuronal ensemble that mediates the behavior. Our functional molecular photoacoustic tomography (FM-PAT) system allows direct imaging of Fos-dependent neuronal ensemble activation in Fos-LacZ transgenic rats in vivo. We tested four experimental conditions and found increased FM-PAT signal in prefrontal cortical areas in rats undergoing conditioned fear or novel context exposure. A parallel immunofluorescence ex vivo study of Fos expression found similar findings. These findings demonstrate the ability of FM-PAT to measure Fos-expressing neuronal ensembles directly in vivo and support a mechanistic role for the prefrontal cortex in higher-order processing of response to specific stimuli or environmental cues.

Water productivity and growth parameters of Fawn-tall fescue and Tekapo-orchard grass under deficit irrigation in arid zones.

This study aimed to determine the drought stress response of Fawn-tall fescue and Tekapo-orchard grass and investigate a drought stress resistance marker. Grass genotypes were grown under four Irrigation treatments I1 equivalent to 0.3 standard crop evapotranspiration (ETc), I2 equivalent to 0.65 ETc, I3 equivalent to 0.75 ETc, and I4 equivalent to 1.2 ETc. Plant height, fresh weight, dry weight were measured and the Water productivity (WP) were calculated. The results showed a reduction in the growth of both grass genotypes as the drought stress increased as indicated by the shorter plants and reduction in fresh and dry weight. However, the WP results showed that the Fawn-tall fescue endured the drought stress better than the Tekapo-orchard grass as indicated by the constant values of the plant WP across the tested irrigation treatments. The results was confirmed by the amplification of dehydrin genes where Fawn-tall fescue was found to be homozygous for dehydrin genes.

Adherence to Good Pharmacy Practices by Community Pharmacies in Lebanon and Opportunities for Quality Improvement: It is Time to Act.

Purpose: Good pharmacy practice is an important standard that highlight the quality of services in community pharmacies. In 2018, The Order of Pharmacists in Lebanon (OPL) published their own good pharmacy practices (GPP) guidelines. The need exists for investigational studies to assess GPP implementation status and the professional conduct of on-site staff towards these standards. Methods: Data collection was carried out between February and August 2020 using a questionnaire covering: Socio-demographic variables; Indicator A (Attitude of the Community Pharmacists); Indicator B (Services and Facilities); Indicator C (Dispensing); Indicator D (Storage). Data analysis were performed on SPSS version 25, T-Test and ANOVA were used. A significant p value of <0.001, 95% confidence interval and variables with missing data counting less than 10% were considered. Results: A total of 211 staffers from pharmacies were enrolled in the study, each representing one community pharmacy. The mean percent of adherence to GPP standards by community pharmacies in the South of Lebanon was below the recommended threshold of 75%. Only 65.09% adhered to all tested indicators (27% to Indicator A, 56.91% to Indicator B, 68.61% to Indicator C, 66.31% to Indicator D). Higher indicators were seen among providers who were aware of OPL standards (OR = 4.021), female (OR= 2.011) and being a licensed pharmacist (OR=3.506). Cronbach alpha of the overall score was 0.615. Conclusion: Further steps shall be taken to improve the compliance to GPP standards. Steps shall include, identification of the core standards, such as dispensing, provision of adequate information, monitoring of storage conditions, and ensuring the presence of a licensed pharmacist. It is highly recommended that the OPL and the Ministry of Public Health develop a "Self-assessment tool" and an efficient training program to increase community Pharmacists' awareness status. Regular assessment shall be carried to monitor the progress overtime.

Public views of community pharmacy services during the COVID-19 pandemic: a national survey.

OBJECTIVE: To assess public opinion about community pharmacy services in Lebanon during the COVID-19 pandemic. METHOD: A cross-sectional study using an online questionnaire was conducted between April and August of 2021. A link was shared randomly among the Lebanese population using WhatsApp and Facebook. Public perceptions were explored within 3 different indicators: general services (B) dispensing (C), and storage (D). Chi-square, Student's test and ANOVA tests were used. p < 0.05 was considered statistically significant. RESULTS: Out of 491 responses, only 9.6% scored above the 75th percentile (19.3% for the general services, 2.4% for dispensing indicator and 12.6% for storage indicator). The main concerns focused on lack of medication and reduced opening hours; however, 67.1% of respondents preferred consulting the community pharmacist instead of visiting primary health care centers, doctor's private clinic and hospitals. Higher mean values of indicators B, C and in the overall indicator were significantly found in the presence of a pharmacist compared to the support pharmacy workforce. CONCLUSION: The overall public perception was inadequate. Significant difference in terms of quality of services was detected in the presence and absence of a community pharmacist during the crisis. It is recommended that the Order of Pharmacist of Lebanon (OPL) and the Ministry of Public Health (MOPH) undergo further steps mainly to enforce the laws concerning dispensing and storage indicators, improve the services in terms of extending the opening hours, ensure the availability of medicines and increase public awareness.

The current trends and challenges towards good community pharmacy practice and the way forward.

Background: The practice of pharmacy continues to evolve. Comprehensive research to monitor and assess the development of the practice is needed. Good Pharmacy Practices (GPP) have been adopted by many countries to enhance the quality of services. Little information is available concerning how pharmacy practices are being implemented in developing countries. Lebanon being a developing country is a good example where community pharmacy practice doesn't follow clear guidelines and no evidence of good clinical practice. Objectives: This study aims to highlight GPP implementation, to identify obstacles impeding implementation, and to suggest how its application could be facilitated in Lebanon. Methods: The review included studies published in English during the last five years covering aspects of pharmacy practice in relation to GPP standards. The search excluded research related to hospital pharmacy practice and primary health care centers since they have their own quality standards. Results: The research identified 20 recent studies that covered aspects of community pharmacy practice in Lebanon in relation to GPP standards. Eight of the studies related to research and professional development,5 related to the provision of medicines,4 related to interaction and communication,1 related to trainees,1 related to pharmacotherapy monitoring, and 1 related to documentation systems. An additional 6 studies provided insight into factors that affect the pharmacy practice in general. It is apparent that the pharmacy practice would benefit if pharmacists were better supported with financial incentives and a readjustment of their working conditions as this would have a positive impact on their productivity, job satisfaction, and overall well-being. The review indicated that the standard of research and professional development was the most studied topic and it was recommended that pharmacists develop their research capabilities. It was observed that there is a tendency towards implementing Continuous Education for pharmacists and obstacles primarily included work and family commitments, lack of interest, lack of time, difficulties in commuting, and lack of competence in the use of technology. This standard is aligned with the FIP's developmental goal of continuing professional development strategies. The search also identified only one pilot study to assess GGP compliance among community pharmacies in Lebanon. This pilot study was limited and showed low adherence of community pharmacies in Lebanon to GPP standards.Barriers to implementation are lack of enforcing laws,inadequate dissemination of the standards among the community pharmacists, poor public perception, and the financial and soscioeconomically crisis facing Lebanon. Conclusion: Collaborated efforts are needed to implement GPP standards in Lebanon.It is recommended to undergo training and awareness sessions to community pharmacists thus enhancing their commitment and motivation. It is also recommended to establish key performance indicators to monitor the implementation. Indicators should include structure indicators for regulating the storage of medications, process indicators for regulating the dispensing, and outcome indicators for reporting patient safety incidents, measuring public satisfaction and the provision and use of medicines.These recommendations can be used by Health authorities and Pharmacy educational institutions in Lebanon and in all similar low-income countries.

Comparison of off-the-shelf ß-tricalcium phosphate implants with novel resorbable 3D printed implants in mandible ramus of pigs.

Facial reconstructive surgery has already implemented the use of 3D printed Patient Specific Implants derived from CAD/CAM-based technologies as an alternative to preformed bone graft substitutes. 3D-printed patient-specific implants derived from CAD/CAM-based technologies are used in facial reconstructive surgery as an alternative to preformed bone graft substitutes. However, to minimize the invasiveness and long-term adverse effects of surgical interventions, the implant needs to exhibit exact fitting, porosity, density, and volume and be made from resorbable materials that allow ingrowth and formation of new bone tissue. Therefore, we present this pilot study using 3D-printed implants consisting of pure ß-TCP, produced using a novel technique that assures these properties. Eight pigs received 3D-printed truncated porous cone bone implants paired with either an off-the-shelve a chronOS (DePuy Synthes chronOS Vivify Preforms) preformed block (n = 4) or a no-implant void (n = 4) in a surgically created defect on each side of the angle of the mandible. After 6 months, CT data showed that all 3D-printed implants performed as well as did the off-the-shelve implants, with predicted osteointegration medially and laterally and with minimal gapping between the implants and native bone. The CT findings were confirmed by histological analysis that revealed that the 3D-printed implants together with the off-the-shelve implants were almost complete resorbed. Much of the resorbed volume had been replaced by vascularized compact bone, and fusion between newly formed bone and native bone was observed in all implants, further indicating that the 3D-printed implants and off-the-shelve implants performed equally well. Only soft tissue developed in the void control sites. Further studies are needed to confirm these initial findings.

Direct measurement of neuronal ensemble activity using photoacoustic imaging in the stimulated Fos-LacZ transgenic rat brain: A proof-of-principle study.

Measuring neuroactivity underlying complex behaviors facilitates understanding the microcircuitry that supports these behaviors. We have developed a functional and molecular photoacoustic tomography (F/M-PAT) system which allows direct imaging of Fos-expressing neuronal ensembles in Fos-LacZ transgenic rats with a large field-of-view and high spatial resolution. F/M-PAT measures the beta-galactosidase catalyzed enzymatic product of exogenous chromophore X-gal within ensemble neurons. We used an ex vivo imaging method in the Wistar Fos-LacZ transgenic rat, to detect neuronal ensembles in medial prefrontal cortex (mPFC) following cocaine administration or a shock-tone paired stimulus. Robust and selective F/M-PAT signal was detected in mPFC neurons after both conditions (compare to naive controls) demonstrating successful and direct detection of Fos-expressing neuronal ensembles using this approach. The results of this study indicate that F/M-PAT can be used in conjunction with Fos-LacZ rats to monitor neuronal ensembles that underlie a range of behavioral processes, such as fear learning or addiction.

Plaque Composition as a Predictor of Plaque Ulceration in Carotid Artery Atherosclerosis: The Plaque At RISK Study.

BACKGROUND AND PURPOSE: Plaque ulceration is a marker of previous plaque rupture. We studied the association between atherosclerotic plaque composition at baseline and plaque ulceration at baseline and follow-up. MATERIALS AND METHODS: We included symptomatic patients with a carotid stenosis of <70% who underwent MDCTA and MR imaging at baseline (n = 180). MDCTA was repeated at 2 years (n = 73). We assessed the presence of ulceration using MDCTA. Baseline MR imaging was used to assess the vessel wall volume and the presence and volume of plaque components (intraplaque hemorrhage, lipid-rich necrotic core, and calcifications) and the fibrous cap status. Associations at baseline were evaluated with binary logistic regression and reported with an OR and its 95% CI. Simple statistical testing was performed in the follow-up analysis. RESULTS: At baseline, the prevalence of plaque ulceration was 27% (49/180). Increased wall volume (OR = 12.1; 95% CI, 3.5-42.0), higher relative lipid-rich necrotic core (OR = 1.7; 95% CI, 1.3-2.2), higher relative intraplaque hemorrhage volume (OR = 1.7; 95% CI, 1.3-2.2), and a thin-or-ruptured fibrous cap (OR = 3.4; 95% CI, 1.7-6.7) were associated with the presence of ulcerations at baseline. In 8% (6/73) of the patients, a new ulcer developed. Plaques with a new ulceration at follow-up had at baseline a larger wall volume (1.04 cm3 [IQR, 0.97-1.16 cm3] versus 0.86 cm3 [IQR, 0.73-1.00 cm3]; P = .029), a larger relative lipid-rich necrotic core volume (23% [IQR, 13-31%] versus 2% [IQR, 0-14%]; P = .002), and a larger relative intraplaque hemorrhage volume (14% [IQR, 8-24%] versus 0% [IQR, 0-5%]; P < .001). CONCLUSIONS: Large atherosclerotic plaques and plaques with intraplaque hemorrhage and lipid-rich necrotic cores were associated with plaque ulcerations at baseline and follow-up.

Strontium ion reinforced bioceramic scaffold for load bearing bone regeneration.

Bone defects in load bearing areas require bone reconstruction with strong biomaterial having mechanical characteristics like cortical bone. Bioceramics are biomaterials that support bone formation as well as provide adequate mechanical properties. A strontium substitution of the bioceramic is expected to further increase its bioactivity by enhancing osteogenesis and protect the bone from osteoclastic resorption. The study involves development, characterization and in vivo testing of a newly developed strontium substituted hydroxyapatite based bioceramic scaffold (SrHAB) with sufficient biomechanical properties. Optimal concentration of strontium ion required for enhanced osteogenic differentiation was identified by comparing three compositions of SrHAB scaffold; namely Sr10HAB, Sr30HAB and Sr50 HAB for their Alkaline phosphatase activity in vitro. The selected Sr10HAB scaffold demonstrated in vivo bone formation with osteogenic differentiation of stromal derived mesenchymal stem cells (MSC) from human and ovine sources in ectopic and ovine models. Thus, Sr10HAB scaffold has a potential for application in load bearing bone requirements of orthopaedics and dentistry.

Mixed cation Ag2S-Tl2S-GeS2 glasses: macroscopic properties and Raman scattering studies.

Mixed cation Ag2S-Tl2S-GeS2 glasses containing 40 and 50 mol% of metal sulfide have been synthesized and analyzed for the first time using thermal analysis, conductivity measurements and Raman spectroscopy. The composition dependences of the ionic conductivity and glass transition temperature T g showed the presence of classical mixed cation effect with the minimum of both glass transition temperature and room temperature conductivity and the activation energy maximum centered at r = Ag/(Tl + Ag) ≈ 0.2. Raman spectroscopy measurements reveal that the structure of the mixed glasses is not a simple mixture of the end-members, pure thallium (r = 0) and silver (r = 1) thiogermanates. The edge-sharing ES-Ge2S6 dimers and corner-sharing CS-Ge n S3n+1 (n = 2 or 3) oligomers disappear more quickly than is predicted by the stoichiometry relations. The systematic evolution of the vibrational properties as a function of the silver fraction r also suggests that the both cations are not separated spatially in the glass network but rather located in close proximity to each other.

Ageing enhances the shedding of splenocyte microvesicles with endothelial pro-senescent effect that is prevented by a short-term intake of omega-3 PUFA EPA:DHA 6:1.

BACKGROUND: Ageing is associated with progressive endothelial senescence and dysfunction, and cardiovascular risk. Circulating endothelial microvesicles (MVs) are pro-senescent and pro-inflammatory endothelial effectors in acute coronary syndrome. Omega-3 PUFA intake was claimed beneficial in cardiovascular prevention. PURPOSE: To investigate whether the intake of the omega-3 formulation EPA:DHA 6:1 by middle-aged and old rats reduces the shedding of pro-senescent microvesicles from cultured spleen leukocytes (SMVs) and clarify the underlying mechanisms in target coronary primary endothelial cells (ECs). METHODS: Middle-aged male Wistar rats (M, 48-week old) received 500 mg/kg/d of either EPA:DHA 6:1, EPA:DHA 1:1, or vehicle (CTL) for 7 days, old rats (72-week old) for 14 days. Spleen-derived leukocytes were prepared and cultured for 24 h and MVs collected from supernatants (SMVs). Cultured ECs were prepared from freshly isolated porcine coronary arteries. Senescence-associated ß-galactosidase activity (SA-ß-gal) was assessed by C12FDG, protein expression by Western blot analysis, oxidative stress by dihydroethidium using confocal microscopy, and procoagulant MVs by prothrombinase assay. The pro-senescent potential of SMVs from middle-aged rats (M-SMVs) was analyzed by comparison with young (Y, 12-week) and old (O) rats. RESULTS: The shedding of SMVs significantly increased with age and was inhibited by EPA:DHA 6:1 intake that also prevented ROS accumulation in spleen. Incubation of ECs with 10 nM SMVs from middle-aged and old but not those from young rats induced premature senescence after 48 h. The pro-senescent effect of M-SMVs was prevented by Losartan and associated with endothelial oxidative stress. M-SMVs induced an up-regulation of senescence markers (p16, p21, p53), pro-atherothrombotic (VCAM-1, ICAM-1, tissue factor) and pro-inflammatory markers (pNF-κB, COX-2) and proteins of the angiotensin system (ACE, AT1-R). Conversely, endothelial NO synthase was down-regulated. Intake of EPA:DHA 1:1 and 6:1 by middle-aged rats decreased SMV shedding by 14% and 24%, respectively. Only EPA:DHA 6:1 intake abolished the M-SMVs-induced endothelial senescence and reduced the pro-senescent action of O-SMVs by 45%. Protection of ECs was not observed in response to SMVs from EPA:DHA 1:1 treated rats. CONCLUSION: Ingestion of EPA:DHA 6:1 by middle-aged or old rats, respectively abolished or limited both the shedding of SMVs and their pro-senescent, pro-thrombotic and pro-inflammatory effects in ECs, most likely by triggering the local angiotensin system. EPA:DHA 6:1 may help to delay ageing-related endothelial dysfunction.

Unawareness of health insurance expiration status among women of reproductive age in Northern Ghana: implications for achieving universal health coverage.

BACKGROUND: Ghana implemented a national health insurance scheme in 2005 to promote the provision of accessible, affordable, and equitable healthcare by eliminating service user fees. Termed the National Health Insurance Scheme (NHIS), its active enrollment has remained low despite a decade of program implementation. This study assesses factors explaining this problem by examining the correlates of insurance status unawareness among women of reproductive age. METHODS: In 2015, a random probability cross-sectional survey of 5914 reproductive-aged women was compiled in the Upper East Region, an impoverished and remote region in Northern Ghana. During the survey, two questions related to the NHIS were asked: "Have you ever registered with the NHIS?" and "Do you currently have a valid NHIS card?" If the answer to the second question was yes, the respondents were requested to show their insurance card, thereby enabling interviewers to determine if the NHIS requirement of annual renewal had been met. Results are based on the tabulation of the prevalence of unawareness status, tests of bivariate associations, and multivariate estimation of regression adjusted effects. RESULTS: Of the 5914 respondents, 3614 (61.1%) who reported that they were actively enrolled in the NHIS could produce their insurance cards upon request. Of these respondents, 1243 (34.4%) had expired cards. Factors that significantly predicted unawareness of card expiration were occupation, district of residence, and socio-economic status. Relative to other occupational categories, farmers were the most likely to be unaware of their card invalidity. Respondents residing in three of the study districts were less aware of their insurance card validity than the other four study districts. Unawareness was observed to increase monotonically with relative poverty. CONCLUSION: Unawareness of insurance care validity status contributes to low active enrollment in Ghana's NHIS. Educational messages aimed at improving health insurance coverage should include the promotion of annual renewal and also should focus on the information needs of farmers and low socio-economic groups.

Thrombospondins Differentially Regulate Proteins Involved in Arterial Remodeling.

Thrombospondins (TSPs) are matricellular glycoproteins expressed in response to vascular injury. TSP-1 and TSP-2 are promotors of arterial remodeling while TSP-5 is believed to be protective. The current study assessed the differential effect of TSPs on protein expression in vascular smooth muscle cells (VSMCs). We hypothesized that TSP-1, TSP-2 and TSP-5 would regulate VSMC proteins involved in arterial remodeling. Human VSMCs were exposed to TSP-1, -2, -5 or serum free media (24 hours). Cell lysates were used to assess the targets TSP-1, TSP-2, TSP-5 and CD44), while the culture media was used to detect TGF-ß1, PDGF-BB, ANGPTL-4 and IL-8. Statistical analysis was performed by t-test and p< 0.05 was considered significant. All TSPs increased their own expression and TSP-5 increased TSP-2. TSP-1 and TSP-2 increased production of ANGPTL-4 and PDGF-BB, while TSP-5 only increased ANGPTL-4. TSP-1 increased exclusively TGF-ß1 and CD44 production. TSP-2 increased TSP-1 expression. All TSPs decreased IL-8. The findings suggest that TSP-1 and TSP-2 may promote vascular remodeling, in part, by increasing ANGPTL-4, PDGF-BB and their own expression. TSP-5 did not upregulate the inflammatory mediators TSP-1, PDGF-BB or TGF-ß1, but upregulated its own expression, which could be a protective mechanism against the response to vascular injury.

An assessment of a performance-based management agreement initiative in Ghana's health service.

BACKGROUND: As part of its efforts to improve efficiency, accountability and overall performance, the Ghana Health Service (GHS) introduced annual Performance-based Management Agreements (PMAs) in the year 2013. However, no assessment of this initiative has since been made in order to inform policy and practice. This paper provides an assessment of this policy initiative from the perspective of managers at various levels of service implementation. METHODS: Mixed methods were employed. Questionnaires were administered to managers through an online survey (using Google forms). Descriptive and inferential statistical methods were used to analyze and present quantitative results while qualitative data was analyzed via thematic analysis. RESULTS: The content and objectives of the PMAs were observed to be comprehensive and directed at ensuring high performance of directorates. Targets of PMAs were found to be aligned with overall health sector objectives and priorities. The directors felt PMAs were useful for delegating task to subordinates. PMAs were also found to increase commitment and contributed to improving teamwork and prudent use of resources. However, PMAs were found to lack clear implementation strategies and were not backed by incentives and sanctions. Also, budgetary allocations did not reflect demands of PMAs. Furthermore, directors at lower levels were not adequately consulted in setting PMAs targets as such district specific challenges and priorities are not usually factored into the process. Insufficient training of staff and lack of requisite staff were key challenges confronting the implementation of PMAs in most directorates. Weak monitoring and evaluation was also observed to significantly affect the success of PMAs. CONCLUSION: There is the need to address the weaknesses and improve on the existing strengths identified by this assessment in order to enhance the effectiveness of PMAs utilization in the Ghana health service.

Ionic-to-Electronic Conductivity Crossover in CdTe-AgI-As2Te3 Glasses: An 110mAg Tracer Diffusion Study.

Conductivity isotherms of (CdTe) x(AgI)0.5- x/2(As2Te3)0.5- x/2 glasses (0.0 ≤ x ≤ 0.15) reveal a nonmonotonic behavior with increasing CdTe content reminiscent of mixed cation effect in oxide and chalcogenide glasses. Nevertheless, the apparent similarity appears to be partly incorrect. Using 110mAg tracer diffusion measurements, we show that semiconducting CdTe additions produce a dual effect: (i) decreasing the Ag+ ion transport by a factor of ≈200 with a simultaneous increase of the diffusion activation energy and (ii) increasing the electronic conductivity by 1.5 orders of magnitude. Consequently, the conductivity minimum at x = 0.05 reflects an ionic-to-electronic transport crossover; the silver-ion transport number decreases by 3 orders of magnitude with increasing x.

Mycothiol acetyltransferase (Rv0819) of Mycobacterium tuberculosis is a potential biomarker for direct diagnosis of tuberculosis using patient serum specimens.

Mycobacterium tuberculosis infection constitutes a global threat that results in significant morbidity and mortality worldwide. Efficient and early diagnosis of tuberculosis (TB) is of paramount importance for successful treatment. The aim of the current study is to investigate the mycobacterial mycothiol acetyltransferase Rv0819 as a potential novel biomarker for the diagnosis of active TB infection. The gene encoding Rv0819 was cloned and successfully expressed in Escherichia coli. The recombinant Rv0819 was purified using metal affinity chromatography and was used to raise murine polyclonal antibodies against Rv0819. The raised antibodies were employed for direct detection of Rv0819 in patient serum samples using dot blot assay and competitive enzyme-linked immunosorbent assay (ELISA). Serum samples were obtained from 68 confirmed new TB patients and 35 healthy volunteers as negative controls. The dot blot assay showed sensitivity of 64·7% and specificity of 100%, whereas the competitive ELISA assay showed lower sensitivity (54·4%) and specificity (88·57%). The overall sensitivity of the combined results of the two tests was found to be 89·7%. Overall, the mycobacterial Rv0819 is a potential TB serum biomarker that can be exploited, in combination with other TB biomarkers, for efficient and reliable diagnosis of active TB infection. SIGNIFICANCE AND IMPACT OF THE STUDY: The early and accurate diagnosis of tuberculosis infection is of paramount importance for initiating treatment and avoiding clinical complications. Most current diagnostic tests have poor sensitivity and/or specificity and in many cases they are too expensive for routine diagnostic testing in resource-limited settings. In the current study, we examined a novel mycobacterial serum biomarker, namely mycothiol acetyltransferase Rv0819. The antigen was detectable in serum specimens of a significant number of tuberculosis patients. This article proves the importance of Rv0819 and paves the way towards its future use as a useful diagnostic marker for tuberculosis infection.

Polypropylene-based composite mesh versus standard polypropylene mesh in the reconstruction of complicated large abdominal wall hernias: a prospective randomized study.

PURPOSE: To compare polypropylene mesh positioned onlay supported by omentum and/or peritoneum versus inlay implantation of polypropylene-based composite mesh in patients with complicated wide-defect ventral hernias. METHODS: This was a prospective randomized study carried out on 60 patients presenting with complicated large ventral hernia in the period from January 2012 to January 2016 in the department of Gastrointestinal Surgery unit and Surgical Emergency of the Main Alexandria University Hospital, Egypt. Large hernia had an abdominal wall defect that could not be closed. Patients were divided into two groups of 30 patients according to the type of mesh used to deal with the large abdominal wall defect. RESULTS: The study included 38 women (63.3 %) and 22 men (37.7 %); their mean age was 46.5 years (range, 25-70). Complicated incisional hernia was the commonest presentation (56.7 %).The operative and mesh fixation times were longer in the polypropylene group. Seven wound infections and two recurrences were encountered in the propylene group. Mean follow-up was 28.7 months (2-48 months). CONCLUSIONS: Composite mesh provided, in one session, satisfactory results in patients with complicated large ventral hernia. The procedure is safe and effective in lowering operative time with a trend of low wound complication and recurrence rates.

Transgelin is a TGFß-inducible gene that regulates osteoblastic and adipogenic differentiation of human skeletal stem cells through actin cytoskeleston organization.

Regenerative medicine is a novel approach for treating conditions in which enhanced bone regeneration is required. We identified transgelin (TAGLN), a transforming growth factor beta (TGFß)-inducible gene, as an upregulated gene during in vitro osteoblastic and adipocytic differentiation of human bone marrow-derived stromal (skeletal) stem cells (hMSC). siRNA-mediated gene silencing of TAGLN impaired lineage differentiation into osteoblasts and adipocytes but enhanced cell proliferation. Additional functional studies revealed that TAGLN deficiency impaired hMSC cell motility and in vitro transwell cell migration. On the other hand, TAGLN overexpression reduced hMSC cell proliferation, but enhanced cell migration, osteoblastic and adipocytic differentiation, and in vivo bone formation. In addition, deficiency or overexpression of TAGLN in hMSC was associated with significant changes in cellular and nuclear morphology and cytoplasmic organelle composition as demonstrated by high content imaging and transmission electron microscopy that revealed pronounced alterations in the distribution of the actin filament and changes in cytoskeletal organization. Molecular signature of TAGLN-deficient hMSC showed that several genes and genetic pathways associated with cell differentiation, including regulation of actin cytoskeleton and focal adhesion pathways, were downregulated. Our data demonstrate that TAGLN has a role in generating committed progenitor cells from undifferentiated hMSC by regulating cytoskeleton organization. Targeting TAGLN is a plausible approach to enrich for committed hMSC cells needed for regenerative medicine application.

Mercury Sulfide Dimorphism in Thioarsenate Glasses.

Crystalline mercury sulfide exists in two drastically different polymorphic forms in different domains of the P,T-diagram: red chain-like insulator α-HgS, stable below 344 °C, and black tetrahedral narrow-band semiconductor ß-HgS, stable at higher temperatures. Using pulsed neutron and high-energy X-ray diffraction, we show that these two mercury bonding patterns are present simultaneously in mercury thioarsenate glasses HgS-As2S3. The population and interconnectivity of chain-like and tetrahedral dimorphous forms determine both the structural features and fundamental glass properties (thermal, electronic, etc.). DFT simulations of mercury species and RMC modeling of high-resolution diffraction data provide additional details on local Hg environment and connectivity implying the (HgS2/2)m oligomeric chains (1 ≤ m ≤ 6) are acting as a network former while the HgS4/4-related mixed agglomerated units behave as a modifier.

Genome-wide mRNA and miRNA expression profiling reveal multiple regulatory networks in colorectal cancer.

Despite recent advances in cancer management, colorectal cancer (CRC) remains the third most common cancer and a major health-care problem worldwide. MicroRNAs have recently emerged as key regulators of cancer development and progression by targeting multiple cancer-related genes; however, such regulatory networks are not well characterized in CRC. Thus, the aim of this study was to perform global messenger RNA (mRNA) and microRNA expression profiling in the same CRC samples and adjacent normal tissues and to identify potential miRNA-mRNA regulatory networks. Our data revealed 1273 significantly upregulated and 1902 downregulated genes in CRC. Pathway analysis revealed significant enrichment in cell cycle, integrated cancer, Wnt (wingless-type MMTV integration site family member), matrix metalloproteinase, and TGF-ß pathways in CRC. Pharmacological inhibition of Wnt (using XAV939 or IWP-2) or TGF-ß (using SB-431542) pathways led to dose- and time-dependent inhibition of CRC cell growth. Similarly, our data revealed up- (42) and downregulated (61) microRNAs in the same matched samples. Using target prediction and bioinformatics, ~77% of the upregulated genes were predicted to be targeted by microRNAs found to be downregulated in CRC. We subsequently focused on EZH2 (enhancer of zeste homolog 2 ), which was found to be regulated by hsa-miR-26a-5p and several members of the let-7 (lethal-7) family in CRC. Significant inverse correlation between EZH2 and hsa-miR-26a-5p (R(2)=0.56, P=0.0001) and hsa-let-7b-5p (R(2)=0.19, P=0.02) expression was observed in the same samples, corroborating the belief of EZH2 being a bona fide target for these two miRNAs in CRC. Pharmacological inhibition of EZH2 led to significant reduction in trimethylated histone H3 on lysine 27 (H3K27) methylation, marked reduction in cell proliferation, and migration in vitro. Concordantly, small interfering RNA-mediated knockdown of EZH2 led to similar effects on CRC cell growth in vitro. Therefore, our data have revealed several hundred potential miRNA-mRNA regulatory networks in CRC and suggest targeting relevant networks as potential therapeutic strategy for CRC.